Impaired pancreatic beta cell function in the fetal GK rat. Impact of diabetic inheritance.
The Goto-Kakisaki (GK) rat is a genetic model of non-insulin-dependent diabetes. At 21.5 d of age we found that GK fetuses had an increased plasma glucose concentration, a decreased plasma insulin level, and a reduced pancreatic beta cell mass. To investigate the beta cell function during fetal life we used a hyperglycemic clamp protocol applied to the mothers, which allowed us to obtain a steady-state hyperglycemia in the corresponding fetuses. At variance, with Wistar (W) fetuses, plasma insulin concentration in GK fetuses did not rise in response to hyperglycemia. In contrast, GK fetal pancreas released insulin in response to glucose in vitro to the same extent as W fetal pancreas. Such a discrepancy between the in vivo and in vitro results suggests that the lack of pancreatic reactivity to glucose as seen in vivo is extrinsic to the fetal GK beta cell. Finally, the importance of gestational hyperglycemia was investigated by performing crosses between GK and W rats. Fetuses issued from crosses between W mother and GK father or GK mother and W father had a beta cell mass close to normal values and were still able to increase their plasma insulin levels in response to hyperglycemia in vivo. Our data suggest that hyperglycemia in utero does not influence the severity of the decrease of the beta cell mass or the lack of the insulin secretory response to glucose in the fetal GK rat. Moreover they indicate that conjunction of GK genes originating from both parents is necessary in order for these defects to be fully expressed.
Serradas
P
P
Laboratoire de Physiopathologie de la Nutrition, CNRS URA 307, Université Paris 7, Denis Diderot, 75 251 Paris Cedex 05, France. serradas@paris7.jussieu.fr
Gangnerau
M N
MN
Giroix
M H
MH
Saulnier
C
C
Portha
B
B
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000196:embryology* / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000196:embryology* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009929:Organ Size; D010179:Pancreas / Q000166:cytology / Q000196:embryology* / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000097:blood; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D007328:Insulin